The theme of this Program Project is to explore, as completely as possible, the correlations between the anatomical, physiological, biochemical and behavioral (clinical) aspects of orofacial (trigeminal) pain transmission and control. This multidisciplinary study of trigeminal pain and analgesic mechanisms will utilize techniques of biochemistry, molecular biology and immunology, in addition to the more traditional techniques of light and electron microscopy, behavioral -pharmacology, physiology and clinical investigation to elucidate pain transmission and analgesia circuits and the development of analgesic therapies in animal and clinical models. Dr. Ralston and Ohara (P-1) using tracing techniques and monoclonal antibodies against neural tissue will characterize nociceptive pathways to higher centers from tooth pulp and oral cavity. Dr. Basbaum (P-2) will study in the central nociceptive pathways, the expression of the proto- oncogene product, c-fos, after noxious stimuli and its modulation by various analgesic agents. Dr. Coderre, Taiwo and Goldyne (P-3) will investigate, in animal models of pain, analgesic synergy of drug combinations selected on the basis of current knowledge of pain control circuits. Drs. Levine and Gordon (P-4) will study analgesic synergy between opiates of different receptor specificity, monoamines, and eicosanoids, using their established model of post-operative dental pain. They will also collaborate with Drs. Coderre, Taiwo and Goldyne in testing, in their clinical model, combinations that provide synergy in animal models. This multidisciplinary approach should significantly increase our understanding of trigeminal pain, as well as provide insights for the effective management of clinical problems of substantial prevalence and morbidity.